We have shown previously that circulating epinephrine increases renin secretion and decreases sodium excretion in the dog kidney, and that these effects appear to be mediated by extrarenal events. The present experiments are designed to define the roles of a number of organ systems and potential mediating factors in epinephrine-induced increases in renin secretion and decreases in sodium excretion. Arterial blood pressure will be kept constant in most of these experiments by means of a constant-pressure blood reservoir system. The first experiments will determine how rapidly a B1-adrenoceptor agonist, prenalterol, can stimulate renin secretion in anesthetized dogs in the absence of changes in blood pressure or renal nerve activity. The potenial roles of the lungs, the heart, and the hindlimb vasculature in epinephrine-induced renin secretion will be tested by comparing the renin secretory responses to infusions of epinephrine directly into these organ systems to responses obtained when epinephrine is infused systemically. The importance of circulating histamine as a mediator of epinephrine-induced renin secretion will be tested by comparing the renin secretory responses to epinephrine before and after total histamine H1- and H2-receptor blockade. Additional experiments are designed to test the possible contributions of changes in venous pressure, and of a possible renin-stimulating factor in blood, to epinephrine-induced increases in renin secretion. Finally, the hypothesis that epinephrine-induced decreases in renal sodium excretion are secondary to increased angiotensin II concentration will be tested in experiments in which converting enzyme inhibitor is used to prevent a rise in angiotensin II concentration during epinephrine infusion. The results may define the connecting links between circulating epinephrine, renin secretion and sodium excretion. Such information may improve our knowledge of the mechanisms whereby blood pressure and fluid volume are controlled.